The D-Biotin, also known as Vitamin H, is mainly applied to the fields of medicine and sanitation, nutrition enhancer, feed additive, cosmetics and drinks, etc. The molecular structural formula of the D-Biotin is shown as follows:

Since the debut of industrially-synthetized D-biotin of a Swiss company Roche in 1949, the synthesis methods have been still undergone many researches abroad. To date, many about total synthesis routes have been reported. Yet, the Sternbach route with thiolactone as a key intermediate still remains the recognition of the most industrial significance.
The Sternbach route includes that thiolactone 2 with optical activity is used as a starting material, the key intermediate (3aR,8aS,8bS)-1,3-dibenzyl-2-oxo-10H-iminazole [3,4-d] thiophene [1,2-a] sulfuryl halide 3 is obtained by several steps of reaction, and with the presence of base, bromide 3 and diethyl malonate are reacted to obtain an intermediate 4, the intermediate 4 is kept treated by hydrobromic acid (including several steps of esterolysis, decarboxylation and debenzylation), and finally the biotin 1 is obtained by cyclization. The Sternbach systhesis route is drawn as follow.

In the condensation process of the bromide 3 and malonic diester, since the malonic diester comprises two reactive hydrogens, when the intermediate 4 is obtained after the malonic diester is reacted with the bromide 3, impurities 5 are also produced in the train of further reaction between the intermediate 4 and the bromide 3 under the action of the base. The impurities 5 are hydrolyzed, decarboxylated, debenzylated and cyclized together with the common intermediate 4, thus, the finally obtained biotin 1 should be doped with impurities 6. Though researchers have successfully attempts to reduce the impurities 6 by increasing proportion of the malonic diester and reduce content of the impurities in the product by a recrystallizing method, yet the impurities are unlikely to be completely removed from the finished biotin. So production of the impurities is a kind of technical defect in this route. Besides, the production mechanism and the chemical formula of the impurities are shown as follow.
